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Options of treatment for childhood cancer
GREGOROVÁ, Tereza
This bachelor thesis focuses on oncological diseases in children and adolescents. It deals with differences between pediatric patients and adults, what are the causes of their malignant diseases, prevention, symptoms and treatment. In the practical part I focused on radiation therapy in children, using photon beam and proton beam, their advantages and disadvantages. I dealt with the incidence of the most common malignancies in children aged 0-19 years in the period 1996-2016. I analyzed the data from the National Cancer Registry and processed it into graphs and tables. I also looked at the data on the long-term survival of cured patients. The collected data show rather a decreasing tendency in the incidence of childhood malignancies in the monitored period 1996-2016. Tumor mortality in children has been decreasing in the period under review, after an initial sharp decline in recent years rather slightly. The higher incidence of malignancies in children aged 0-19 is in boys. I also graphically processed the age distribution of patients, where the first wave of increased incidence is recorded in the youngest patients under 4 years and the second wave in adolescents aged 15-19 years, which is different from the distribution of tumor incidence in the adult population where the risk of cancer increases with age. The relative percentage of five-year survival in pediatric cancer patients over time has increased with the development of cancer treatment and supportive care and dispenzarzation. The content of this work can serve as a basic overview of cancer of children and adolescents for health professionals and the general public.
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Imunoterapie metastazujícího pankreatického adenokarcinomu řešená na dvounádorovém modelu
SKALIČKOVÁ, Markéta
This master's thesis studies the efficacy of cancer immunotherapy based on TLR agonists and ligands stimulating phagocytosis, abbreviated as MBTA therapy, using a mouse model of pancreatic adenocarcinoma. The main goals are: (1) to enhance the efficacy of MBTA in the case of large tumors, (2) to enhance the efficacy of MBTA using a bilateral pancreatic adenocarcinoma mouse model, (3) to examine the potential of lipoteichoic acid to opsonize cancer cells and stimulate phagocytic cells.
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The importance of immunogenic cell death for modern tumor immunotherapy
Kubešová, Kateřina ; Šírová, Milada (advisor) ; Adkins, Irena (referee)
Immunogenic cell death is characterized by the release of molecules with damage-associated molecular patterns which can subsequently activate immune system. Only specific types of cell death can release these molecules. Classification of immunogenic cell death types and understanding of their initiation can be used for activation of the immune system against cancer cells. Simultaneously, it is necessary to understand different mechanisms, how the molecules with damage-associated molecular patterns work. Molecules with damage-associated molecular patterns which are studied the most, not only for their use in anticancer therapy, are type I interferons, calreticulin, high mobility group box 1 protein and heat shock proteins 70 and 90. Key words: immunogenic cell death, molecules with damage-associated molecular patterns, cancer, immunotherapy, type I interferons, calreticulin, high mobility group box 1 protein, ATP, heat shock protein 70, heat shock protein 90
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The significance of physiotherapy after the surgeries of tumoral processes through the thoracic way
Hrbáčková, Karolína ; Zadražilová, Gabriela (advisor) ; Smolíková, Libuše (referee)
Tumoral diseases of the lungs are one of the most frequent causes of hospitalization and necessary surgical interventions in the chest area. The most common is bronchogenic carcinoma, which is mentioned as the most common malignancy among men in incidence and mortality. In women it occupies the third place. Worldwide, it results in 20% of all deaths from oncological causes. The main theoretical part of this bachelor's thesis is focused on the possibilities of physiotherapy with patients after chest surgery emphasizing respiratory physiotherapy. Part of the practical section of this bachelor's thesis reviews questionnaires distributed to the patients with the aim of analyzing patient participation, the quality of and satisfaction with their preoperative and early postoperative rehabilitation and interest in outpatient rehabilitation. A case report of a patient who underwent chest surgery due to a lung cancer is added.
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Cancer as a source of fright and how patiens with tumour illness learn to work with their illness
Spíralová, Anna ; Grygar, Jakub (advisor) ; Hájek, Martin (referee)
This thesis is focused on an important problem of today, which is cancer. It describes this deceitful sickness from social point of view, suggesting what impact cancer has on living in a society and on the position of the sick people inside the society. Cancer is connected with strong connotations, which are constructed by the media and society's point of view. It is primarily the status of a "fighter", which is a dominant consensus for communication inside a family and for the view of the cancer patient. Patient with cancer, alias "fighter" is a men, who has cancer, but doesn't stop being active, he fights with cancer and doesn't forgot his live. He works and has social life and etc. This behavior is expected from him by his family and close people, but cancer is a sickness, which .causes pain and fears about patient's own life very often, so the cancer patient must struggle not only with the sickness, but also with fulfilling the expectations of the role of the "fighter" for his or her close people. Next will be shown, how the patients work with the cancer and how they learn to be patients and how the cancer shapes their lives and how they include it in their biography as a very important experience in their life and how they connect the birth of the cancer, which is not known very well, with the...
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The role of mitochondrial complex II in cancer cell biology
Kraus, Michal ; Neužil, Jiří (advisor) ; Kašpárek, Petr (referee)
Mitochondria are essential organelles for most eukaryotic cells, containing intricate networks of numerous proteins. These include, among others, complexes I-IV of the electron transport chain. Being at the crossroads of the tricarboxylic acid cycle and the respiratory chain, mitochondrial complex II plays a key role in cellular metabolism. The protein complex, also known as succinate dehydrogenase, is capable of not only succinate oxidation and electron transfer but also contributes to the production of reactive oxygen species. Mitochondrial complex II consists of four subunits, SDHA-D, and four dedicated protein assembly factors SDHAF1-4 that participate in complex II biogenesis. Mutations and epigenetic modulations of genes coding for succinate dehydrogenase subunits or assembly factors are associated with pathological conditions such as neurodegenerative diseases, or may result in tumor formation. However, inborn complex-II-linked mitochondrial pathologies are rather understudied, compared to diseases with causative errors of other mitochondrial complexes, presumably due to the fact that none of complex II subunits is encoded in the mitochondrial genome. Recent studies have shown that impairment of mitochondrial complex II function or assembly leads to accumulation of alternative assembly forms...
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Metabolism of vandetanib by cytochrome P450 expressed in prokaryotic systems
Rodová, Marie ; Indra, Radek (advisor) ; Takácsová, Paulína (referee)
1 Abstract Recently, biologically targeted treatment by another name targeted molecular therapies have begun to be used in the treatment of cancers bearing specific molecular genetic or morphological traits. Vandetanib is an oral anticancer drug that belongs to a group of tyrosine kinases inhibitors. These inhibitors block signal pathway receptors, thereby inhibit growth, stimulate cell death and reduce the spread of cancer. Vandetanib was approved in April 2011 by the US FDA for a treatment of progressive or symptomatic medullary thyroid cancer. It is used in patients with metastatic or inoperable locally advanced cancer. The metabolism of vandetanib was studied in this thesis. Specifically, the kinetics of vandetanib oxidation to N-desmethylvandetanib by human recombinant cytochromes P450 3A4 expressed in the membrane of E. coli (Bactosomes). The effect of the presence of cytochrome b5 and the effect of the level of NADPH: cytochrome P450 reductase activity on the activity of cytochrome P450 3A4 were studied. The demethylated metabolite of vandetanib, N-desmethylvandetanib, was identified and separated by high performance liquid chromatography (HPLC). Enzyme kinetics studies indicate that vandetanib oxidation is affected by both, the level of NADPH:CYP reductase activity and the presence of cyt b5....
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Analysis of chemotherapeutics in extracellular vesicles
Kožnarová, Simona ; Hložková, Michaela (referee) ; Vašinová Galiová, Michaela (advisor)
Extracellular vesicles are a newly discovered way of cell-to-cell communication. The issue is still significantly unexplored, especially in the case of cancer. The goal of this pilot study was to attempt to detect platinum contained in extracellular vesicles by ICP-MS. In this study, samples of ovarian cancer cell lines treated with platinum derivatives, a type of chemotherapeutic drug, were used. This method was proved as able to detect platinum, even as able to determine its concentration reliably. The quantity of platinum in vesicles was around 1–2 % of the total platinum added to the system. The results varied according to the used platinum derivative, the cell line and the number of cells releasing the vesicles. Most platinum was determined in vesicles of the SK-OV-3 line, which is naturally resistant to this treatment, for all platinum derivatives. From these results it can be concluded that the use of ICP-MS is also advisable for additional research on this issue.
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Use of polymer prodrugs containing cucurbitacin D for the treatment of experimental tumors
Hrabánková, Klára ; Šírová, Milada (advisor) ; Grobárová, Valéria (referee)
Chemotherapy is still the most widely used anti-cancer treatment. The majority of chemotherapeutics inhibit proliferating cells generally, not selectively cancer cells. The side effects associated with chemotherapy can be partly limited by conjugating a cytotoxic drug with a polymer nanocarrier. Such binding facilitates solubility in aqueous solutions, reduces systemic toxicity; and passively targets the drug directly into the tumour through the enhanced permeability and retention (EPR) effect. This thesis focuses on testing polymer conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) carrying cucurbitacin D (CuD), a naturally occurring compound with potential anti-cancer activity. The mechanism of action is not elucidated yet, but several studies have depicted the inhibitory effect on signal transducer and activator of transcription 3 (STAT3) transcription factor. A STAT3 signalling pathway is overexpressed in several cancer cell lines and is also involved in the differentiation of myeloid- derived suppressor cells (MDSCs). We examined the therapeutic effect of the HPMA copolymers based on CuD in combined therapy with other polymer chemotherapeutics. CuD conjugates have shown in vitro cytotoxic effect on several model cancer cell lines. The combination with conjugates carrying doxorubicin...
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Biological effects of edible algae.
Vaňková, Kateřina
Nutritional factors with antioxidant properties, such as those contained in edible algae or green plants, might be implicated in protection against cancer development. Chlorophyll and other tetrapyrrolic compounds, structurally related to heme and antioxidant bile pigment bilirubin, belong to important candidate molecules, which might be responsible for these effects. Based on our studies demonstrating antiproliferative effects of S. platensis edible alga extract on experimental model of human pancreatic adenocarcinoma we investigated in detail the effect of chlorophyll occurring abundantly in this alga. Since only scarce data exist on the antiproliferative effects of chlorophylls, the aim of our study was to assess these effects. The study was performed on experimental models of human pancreatic and prostate cancer. The inhibitory effects of chlorophylls (chlorophyll a, chlorophyll b, chlorophyllin and pheophytin a) on cell proliferation and cell viability were investigated in in vitro studies. Chlorophylls reduced the mRNA expression as well as activity of hemeoxygenase in tested pancreatic cancer cells. Simultaneously, chlorophylls played an important role in redox environment of studied cancer cell lines including modulation of mitochondrial membrane potential, reactive oxygen species (ROS)...
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